The control of acid-base regulation by the kidney is critical in maintaining body electrolyte homeostasis. The inner medullary collecting duct (IMCD) has been shown to be an important nephron site where a significant amount of acid found in the urine is secreted and where the steepest pH gradients are found. The purpose of these studies is to clarify the mechanisms and modulators of acid secretion along the IMCD. In this proposed research we will utilize the complementary techniques of in vivo IMCD microcatheterization and in vitro IMCD cell culture and morphologic analysis to explore the effect of acidification adaptation, renal insufficiency, aldosterone and potassium on IMCD acidification. We will explore the likelihood that there are 2 distinct cell types along the IMCD which have different acid secreting characteristics. We will determine the presence and quantitative importance of the proton pump, the Na+/H+, the HCO3-/C1 and Na+-HCO3- transporters on cell pH regulation. These studies will provide significant new information regarding IMCD acidification.